1. Chapter 15: The Chromosomal Basis of Inheritance

2. Essential Knowledge
3.a.4 – The inheritance pattern of many traits cannot be explained by simple Mendelian genetics (15.1, 15.2, 15.3, 15.5).
3.c.1 – Changes in genotype can result in changes in phenotype (15.4).

3. Sutton (1902) Developed the “Chromosome Theory of Inheritance”
1) Mendelian factors or alleles are located on chromosomes
2) Chromosomes segregate and show independent assortment

5. Morgan Embryologist at Columbia University
Chose to use fruit flies as a test organism in genetics
Allowed the first tracing of traits to specific chromosomes

6. Fruit Fly Drosophila melanogaster Feeds on fungus growing on fruit
Early test organism for genetic studies

7. Reasons he chose fruit fly
Small
Cheap to house and feed
Short generation time
New generation every 2 weeks
100s of offspring produced
Few chromosomes
4 pairs (8 total)
3 pairs autosomes, 1 pair sex

8. Genetic Symbols Mendel: use of uppercase or lowercase letters
T = tall
t = short
Morgan: symbol from the mutant phenotype
+ = wild phenotype (natural pheno)
No symbol = mutant phenotype (any pheno different from wild)

9. Examples Recessive mutation: w = white eyes w+ = red eyes
Dominant mutation:
Cy = Curly wings
Cy+ = Normal wings
Letters come from 1st
mutant trait observed

10. Morgan Observed: Same as Mendel’s F1
A male fly with a mutation for white eyes
Then, he crossed the white eye male with normal red eye female
All had red eyes
Same as Mendel’s F1
This suggests that white eyes is a genetic recessive

11. F1 X F1 = F2 Morgan expected the F2 to have a 3:1 ratio of red:white
He got this ratio
However, all of the white eyed flies were MALE
Most red eyed flies were FEMALE
Therefore, the eye color trait appeared to be linked to sex

12. Morgan discovered: Sex-linked traits
Genetic traits whose expression are dependent on the sex of the individual
Genes on sex chromosomes exhibited unique patterns

13. Eye color gene located on X chromo (with no corresponding gene on Y)

14. Morgan Discovered
There are many genes, but only a few chromosomes
Therefore, each chromosome must carry a number of genes together as a “package”
There was a correlation between a particular trait and an individual’s sex

15. Linked Genes
Traits that are located on the same chromosome (that tend to be inherited together)
Result:
Failure of (deviation from) Mendel's Law of Independent Assortment.
Ratios mimic monohybrid crosses.

16. Body Color and Wing type

17. Body color and wing type
Wild: gray and normal (dom +)
Mutant: Black and vestigal (rec)
This is why we use “b” for body color alleles and “vg” for wing alleles
Symbols:
Body color - b+: gray; b: black
Wings - vg+: normal; vg: vestigal

18. b+b vg+vg X bb vgvg Example #1: b+b = gray; vg+vg = normal
#2: bb = black; vgvg = vestigal
(b+ linked to vg+)
(b linked to vg)
If unlinked: 1:1:1:1 ratio.
If linked: ratio will be altered

22. Crossing-Over Occurs during Pro I of meiosis
Breaks up linkages and creates new ones
Recombinant offspring formed that doesn't match the parental types

23. If Genes are Linked: Independent Assortment of traits fails
Linkage may be “strong” or “weak”

24. Linkage Strength Weak - farther apart Strong - closer together
Degree of strength related to how close the traits are on the chromosome
Weak - farther apart
Strong - closer together
Usually located closer to centromere

25. Genetic Maps Constructed from crossing-over frequencies
1 map unit = 1% recombination frequency
Have been constructed for many traits in fruit flies, humans and other organism.

27. Sex Linkage in Biology Several systems are known: Mammals – XX and XY
Diploid insects – X and XX
Birds – ZZ and ZW
Haploid-Diploid

28. Sex Linkage in Biology Mammals Diploid insects Birds Haploid-Diploid
Determined by whether sperm has X or Y
Diploid insects
Only X chromosomes present
Birds
Egg determines sex
Haploid-Diploid
Females develop from fert egg
Males develop from unfert egg

30. Chromosomal Basis of Sex in Humans
Sex determination ALWAYS 50-50
X chromosome - medium sized chromosome with a large number of traits
Y chromosome - much smaller chromosome with only a few traits

31. Human Chromosome Sex Eggs – only contain X Sperm – either X or Y
Males - XY Females - XX
Comment - The X and Y chromosomes are a homologous pair, but only for a small region at one tip

34. Sex Linkage Inheritance of traits on the sex chromosomes
NOT TO BE CONFUSED WITH sex-linked traits!!!!!
X Linkage - common; Y- rare
Dads: only to daughters (b/c dads ONLY give X chromo to daughters)
Moms: to either sex

35. Males Hemizygous - 1 copy of X chromosome
Show ALL X traits (dominant or recessive)
More likely to show X recessive gene problems than females

36. X-linked Disorders and Patterns
Disorders on X-chromo:
Color blindness
Duchenne's Muscular Dystrophy
Hemophilia (types a and b)
Patterns
Trait is usually passed from a carrier mother to 1 of 2 sons
Affected father has no affected sons, but passes the trait on to all daughters (who will be carriers for the trait)

37. Comment
Watch how questions with sex linkage are phrased:
Chance of children?
Chance of males?
Chance of females?
You MUST practice genetics problems w/ these traits: Hemophilia, Muscular dystrophy and colorblindness (they all work the same!)

38. Can Females be color-blind?
Yes!!!
ONLY if their mother was a carrier and their father is affected
How? Mother contributes X (with affected allele) and dad contributes all he can to make a daughter – affected X

40. 25 29
Are you color blind? 45 56 6 8

41. Y-linkage Hairy ear pinnae
Comment - new techniques have found a number of Y-linked factors that can be shown to run in the males of a family
Ex: Jewish priests

42. Sex Limited Traits Traits that are only expressed in one sex
Ex: prostate development, gonad specialization, fallopian tube development

43. Sex Influenced Traits
Traits whose expression differs because of the hormones of the sex
Ex: beards, mammary gland development, baldness
Baldness:
Testosterone – makes the trait act as a dominant
No testosterone – makes the trait act as a recessive
Males – have gene = bald
Females – must be homozygous to have thin hair (rare)

44. X chromosome inactivation
In every somatic cell (in females), one X chromosome is inactivated
Humans: differs/random
Kangaroos: always paternal X that is inactivated
Called Barr bodies

45. Barr Body Inactive X chromosome observed in the nucleus
Becomes inactive during embryonic development
Way of determining genetic sex (without doing a karyotype)

46. Barr body description
Compact body which lies close to nuclear envelope
Most genes on this X are NOT expressed
Inside developed ovaries, these are reactivated (so that each ova will get an active X)

47. Lyon Hypothesis Which X inactivated is random
Inactivation happens early in embryo development by adding CH3 groups to the DNA
Changes DNA nucleotide
Result - body cells are a mosaic/combo of X types
Some have active X from mom, others active X from dad

48. Examples
Calico Cats
Human examples are known (sweat gland disorder)

49. Question? Why don’t you find many calico males?
They must be XB XOY and are always sterile
Why?
They MUST have an extra X chromo (to have an inactive X - you must have TWO!)

50. Chromosomal Alterations
Two types of alterations:
Changes in number
Changes in structure

51. Number Alterations
Aneuploidy - too many or too few chromosomes, but not a whole “set” change
Polyploidy - changes in whole “sets” of chromosomes

52. Aneuploidy Caused by nondisjunction
the failure of a pair of chromosomes to separate during meiosis
Result: too many or too few chromosomes in a gamete
Nondisjunction in Meiosis I produces 4 abnormal gametes.
Nondisjunction in Meiosis II produces 2 normal and 2 abnormal gametes.

54. Types of Aneuoploidy Monosomy: 2N – 1 (very rare)
Mono = one (missing copy)
Trisomy: 2N + 1 (more common)
Tri = three (extra copy)
Normal: 2N

55. Turner Syndrome Monosomy 2N - 1 or 45 chromosomes
Genotype: X_ or X0
Phenotype: female, but very poor secondary sexual development.
Characteristics:
Short stature.
Extra skin on neck.
Broad chest.
Usually sterile
Normal mental development except for some spatial problems.

58. Question Why are Turner Individuals usually sterile?
Odd chromosome number
Two X chromosomes needed for ovary development.

59. Other Sex Chromosome changes
Kleinfelter Syndrome
Meta female
Supermale

60. Kleinfelter Syndrome Trisomy 2N + 1 (2N + 2, 2N + 3)
Genotype: XXY (XXXY, XXXXY)
Phenotype: male, sexual development may be poor/slow
Often taller than average, mental development fine (in XXY), usually sterile
More X = more mental problems

63. George Washington May have been a Kleinfelter Syndrome individual.
Much taller than average
Produced no children/sterile individual

64. Meta female Trisomy 2N + 1 or 2N + 2 Genotype: XXX or XXXX
Phenotype: female, but sexual development poor.
Mental impairment common.

65. XYY Syndrome OR Super male
Trisomy
2N + 1 or 2N + 2
Genotype: XYY or XYYY
Phenotype: male, usually normal development, fertile w/ normal sex organ development

67. Trisomy events Trisomy 21: Down Syndrome Trisomy 13: Patau Syndrome
Both have various physical and mental changes

68. Down’s

69. Down’s Syndrome Increases with maternal age (especially above 35)
How? An embryo’s ovaries are halted in meiosis I (during egg development)
When ovulation occurs, the eggs resume meiosis and nondisjunction occurs then
This is why it is often seen more in older women
Mental retardation
Heart defects
Characteristic facial features

70. Patau

71. Question? Why is trisomy more common than monosomy?
Fetus can survive an extra copy of a chromosome, but being hemizygous for somatic cell is usually fatal
Why is trisomy 21 more common in older mothers?
Maternal age increases risk of nondisjunction

72. Polyploid Triploid= 3N Tetraploid= 4N Usually fatal in animals
Cells receive AN ENTIRE EXTRA COPY of all homologous chromosomes (including sex chromo)

73. Question?
In plants, even # polyploids are often fertile, while odd # polyploids are sterile.
Why?
Odd number of chromosomes can’t be split during meiosis to make spores.

74. Chromosome Structure Alterations
Deletions: loss of genetic info
Duplications: extra copies of genetic info
Inversions and translocations:
Position effects: a gene's expression is influenced by its location to other genes

76. Cri Du Chat Syndrome Part of p arm of #5 missing
Deletion chromosomal abnormality
Good survival rate
Severe mental retardation
Small sized heads common
Malformed larynx w/ vocal/speech problems

77. Cri du chat

78. Fragile X Part of X chromo is missing Sterile Mental retardation
Deletion
Sterile
Mental retardation
Oversized testes (if male); ovaries (if female)
“Double jointedness”

80. Philadelphia Chromosome
Caused by translocation
An abnormal chromosome produced by an exchange of portions of chromosomes 9 and 22
Causes chronic myeloid leukemia

82. Parental Imprinting of Genes
Gene expression and inheritance depends on which parent passed on the gene
Usually caused by different methylations of the DNA
CAUSE:
Imprints are "erased" in gamete producing cells and re-coded by the body according to its sex
RESULT:
Phenotypes don't follow Mendelian Inheritance patterns because the sex of the parent does matter

83. Example: Both lack a small gene region from chromosome 15
Prader-Willi Syndrome and Angelman Syndrome
Both lack a small gene region from chromosome 15
Male gene contribution missing: Prader-Willi Female: Angelman

86. Why have parental imprinting?
Method that cells might use to detect that TWO different sets of chromosomes are in the zygote

87. Extranuclear Inheritance
Inheritance of genes not located on the nuclear DNA
Where does it come from?
DNA in organelles (Mitochondria and chloroplasts)
Result:
Mendelian inheritance patterns fail.
Maternal Inheritance of traits where the trait is passed directly through the egg to the offspring

88. Mitochondria Myoclonic Epilepsy Ragged Red-fiber Disease
Leber’s Optic Neuropathy
All are associated with ATP generation problems and affect organs with high ATP demands
Muscle, brain

89. Chloroplasts Gives non-green areas in leaves
Called variegation
Several different types known
Very common in ornamental plants

90. Examples

91. Summary
Recognize the relationships between Mendelian inheritance patterns and chromosomes.
Identify linked genes and their effect on inheritance patterns.
Recognize the chromosomal basis of recombination in unlinked and linked genes.
Recognize how crossover data is used to construct a genetic map.
Identify the chromosomal basis of sex in humans.
Recognize examples of sex-linked disorders in humans.

92. Summary Continued Identify X-inactivation and its effect in females.
Recognize sources and examples of chromosomal alterations in humans.
Identify examples of abnormalities in sex chromosome number in humans.
Recognize the basis and effects of parental imprinting of genes in human inheritance patterns.
Recognize the basis and effect of extranuclear inheritance on genetic inheritance patterns.